1. Field of the Invention
The present invention relates generally to treating individuals with ionizing radiation and other treatments of disease.
2. Related Art
The permanent damage caused by ionizing radiation is generally believed to be directly proportional to the dose of radiation. However, an increasing body of evidence has suggested that this model is not appropriate for estimating permanent damage from low dose radiation (LDR) exposure. In fact, the growing body of evidence indicates that LDR induces protection against subsequent high dose ionizing radiation (HDR) exposure. For example, a number of epidemiology studies have shown lower cancer rates for individuals exposed to low doses of radiation (see Cohen, B. L., Health Phys., 68:157-174, 1995; Miller. et al., N. Engl. J. Med., 321:1285-1289, 1989; Cardis et al., Radiat. Res. 142:117-132, 1995). These epidemiological results are supported by in vitro studies that show LDR exposure reduces damage from high-dose radiation (HDR) exposures (referred to in the art as radio-adaptation or hormesis).
The concept of radio-adaptation was first explored in vitro by Olivieri et al., who showed that lymphocytes that had been chronically LDR irradiated were less susceptible to chromatid aberrations from subsequent high dose x-ray exposure (see Olivieri et al., Science, 223:594-597 1984). This finding was confirmed for acute LDR, i.e. short term exposures low dose x-radiation, where LDR-exposed cells, following HDR exposure, showed enhanced survival and fewer chromosome breaks than controls (see Wolff, S., Mutation Research, 358:135-142, 1996).
Results from other studies are consistent with these findings (see Azzam et al., Radiat. Res., 138 (1 Suppl):S28-31, 1994; Azzam et al., Radiat. Res., 146(4):369-73,1996; Shadley et al., Radiation Research, 111(3):511-517, 1987.; Shadley and Wolff, Mutagenesis, 2(2):95-6, 1987; Shadley and Wiencke, Int. J. Radiat. Biol., 56(1):107-118, 1989; and Sanderson and Morley, Mutat. Res., 164(6):347-51, 1986). As a result, it is increasingly becoming accepted that LDR exposures triggers protective cellular mechanisms that induce a radio-adaptive response (e.g. reduce the killing rate of ionizing high dose radiation). In other words, LDR exposure that triggers these protective cellular mechanisms can impede the ability to effectively treat target cells with a subsequent lethal dose of HDR. However, the inventors of the present invention have recently discovered, contrary to what is taught in the biomedical literature, that under certain conditions, LDR and other stressors may be used to increase the killing rate of HDR therapeutic exposures.